This career development award application for Dr. Christie Hartman, sponsored by Dr. Christian Hopfer, describes a 5-year, comprehensive training and research program to obtain skills in genome-wide association studies (GWAS) and examine the genetic contributions to substance dependence and impulsive/risky behavior. Young adults with a history of substance use disorders (SUDs) and antisocial behavior often show impulsive and risk-taking behavior. Studies have shown that genetic factors play a strong role in SUDs and antisocial behavior, and that a heritable impulsive/risky behavior factor underlies the comorbidity between these disorders. Recently, GWAS has become the most powerful way to search for genes involved in these disorders. However, no studies have utilized GWAS to examine SUDs and impulsive/risky behavior. This proposal includes four specific research aims, which are: 1) Conduct a GWAS analysis that examines alcohol consumption using publicly available data, 2) utilizing GWAS data from an ongoing project, conduct a GWAS examining substance dependence and impulsive/risky behavior, 3) recruit 300 young adult probands with symptoms of persistent antisocial substance dependence, and 4) in the newly collected sample, replicate the GWAS findings from Aim 2. Training components include readings, coursework, workshops, and mentorship in the areas of data/GWAS analysis, genotyping, and molecular genetic theory/methods. The purpose of the proposed training and research plans is to 1) provide training in GWAS methods and analysis, 2) provide training in study design and implementation, and 3) create a new sample with which to replicate the GWAS findings. These activities will provide training and skills in new areas, answer important scientific questions, and generate a new sample to use in future R01 proposals, thus creating a platform for future independence. PUBLIC HEALTH RELEVANCE: Young adults with a history of substance abuse and impulsive/risky behaviors experience greatly increased morbidity and mortality compared to the rest of the population, and the resulting costs to society are high. Thus, the identification and characterization of genes involved in these behaviors would facilitate the prevention and treatment of substance-related problems.